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Insulin Resistance and Testosterone in Women

This study has been completed.
Sponsor:
Collaborators:
The John A. Hartford Foundation
University of Pennsylvania Diabetes and Endocrinology Research Center (DERC)
TAP Pharmaceutical Products Inc.
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00123110
First received: July 19, 2005
Last updated: March 9, 2010
Last verified: March 2010
  Purpose

The purpose of this research study is to determine if a relationship between insulin resistance (IR) and testosterone (T) exists in women who have already gone through menopause.


Condition Intervention Phase
Insulin Resistance
Postmenopause
Drug: metformin
Drug: leuprolide acetate
Drug: placebo pill
Drug: placebo injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Free testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
  • Insulin resistance [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), estradiol, total testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
  • Homeostasis model assessment index of insulin resistance (HOMA-IR) [ Time Frame: baseline 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
  • Lipid profile including high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), total cholesterol [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Systolic (SBP) and diastolic (DBP) blood pressure [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
  • Free T and IR in women in whom Metabolic Syndrome (MetSyn, as defined by updated NCEP ATP III criteria) is present vs. those in whom MetSyn is absent [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
  • Dehydroepiandrosterone sulfate (DHEA-S) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Surrogate measures of adiposity including body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: July 2005
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
metformin plus placebo injection
Drug: metformin
Initiated on 500 mg daily and titrated up to 1000 mg twice a day during the first four weeks, remaining at that dose until 12 weeks
Other Name: Glucophage
Drug: placebo injection
matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)
Experimental: 2
leuprolide plus placebo pill
Drug: leuprolide acetate
3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks)
Other Name: Lupron
Drug: placebo pill
matching pill twice a day for 12 weeks
Placebo Comparator: 3
placebo pill plus placebo injection
Drug: placebo pill
matching pill twice a day for 12 weeks
Drug: placebo injection
matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)

Detailed Description:

This study tests the central hypothesis that insulin resistance (IR) increases androgen (male sex hormone) production in postmenopausal women. Participation will include five visits, each lasting on average 2.5 hours, over a period of 13-20 weeks.

At the screening visit, the participant's medical history, current use of medications and dietary supplements, and social habits will be recorded. This information will be reviewed on each subsequent visit; participants are asked to maintain their current diet and physical activity level throughout the study.

A brief physical exam will be performed, and blood will be drawn.

At the 2nd (baseline) visit, patients will undergo a euglycemic-hyperinsulinemic clamp (a procedure to measure insulin sensitivity by continuous intravenous infusion of insulin, and variable infusion of glucose). Blood samples will be drawn throughout the procedure. At completion, the insulin infusion will be stopped, participants will be fed, and the glucose infusion continued for at least 15 minutes to ensure stability of the blood glucose concentration. After the procedure, participants will be randomized to receive either metformin plus leuprolide placebo, leuprolide plus metformin placebo, or metformin placebo plus leuprolide placebo. The leuprolide or leuprolide placebo will be administered as an injection by a nurse. The metformin or metformin placebo will be dispensed to the participant in the form of pills, with instructions for titrating the dose. Participants will be contacted by telephone once weekly during the titration period to assess drug tolerability and adverse events (AEs). Participants will be maintained at their maximum tolerated dose for the duration of the study intervention period.

Participants will return every 4 weeks for follow-up. Blood will be drawn, the nurse will administer the leuprolide or leuprolide placebo injection, and metformin or metformin placebo will be dispensed. At the final visit (week 12), participants will undergo a brief physical exam, and will then undergo a final euglycemic-hyperinsulinemic clamp.

  Eligibility

Ages Eligible for Study:   50 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal women aged 50-79 years with absence of menses for 12 months; for women 50-54 years, FSH>30 mIU/mL to confirm postmenopausal status
  • At least one intact ovary
  • Free testosterone and fasting insulin levels within required study parameters
  • Willing to comply with all study-related procedures
  • Capable of giving informed consent

Exclusion Criteria:

  • History of cancer requiring treatment within the past 5 years (exceptions may be made by investigator)
  • Hospitalization for treatment of vascular disease in the past 6 months
  • Uncontrolled hypertension
  • Hospitalization for chronic obstructive pulmonary disease or asthma in the past 3 months
  • Use of continuous oxygen at home
  • Surgery in the last 30 days
  • Positive for HIV
  • Abnormal blood tests (hemoglobin, fasting triglycerides, fasting glucose, creatinine, liver function)
  • History of diabetes mellitus or use of any anti-hyperglycemic medication in the past 3 months
  • Disease associated with disordered glucose metabolism (Cushing's disease, acromegaly, pheochromocytoma not surgically cured, chronic pancreatitis)
  • History of chronic renal insufficiency
  • Intravenous (IV) contrast studies with iodinated materials planned for the 12 week intervention period that cannot be postponed according to the participant's primary care provider
  • Acute or chronic metabolic acidosis
  • History of liver disease
  • Congestive heart failure
  • History of androgen-secreting tumors
  • Hormone replacement therapy or antiandrogen use in past 6 months
  • Use of DHEA or other androgen-containing products in past 6 months
  • Corticosteroid use, other than topical, ophthalmic, intraarticular, and inhaled preparations, in past 3 months
  • Undiagnosed current vaginal bleeding
  • Excessive alcohol intake, either acute or chronic; current illicit substance abuse
  • Participation in an investigational drug study within 6 weeks prior to screening visit
  • Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient's safety or successful participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00123110

Locations
United States, Pennsylvania
University of Pennsylvania Clinical and Translational Research Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
The John A. Hartford Foundation
University of Pennsylvania Diabetes and Endocrinology Research Center (DERC)
TAP Pharmaceutical Products Inc.
Investigators
Principal Investigator: Anne R. Cappola, MD, ScM University of Pennsylvania
  More Information

Publications:
Responsible Party: Anne R. Cappola, MD, ScM, University of Pennsylvania School of Medicine
ClinicalTrials.gov Identifier: NCT00123110     History of Changes
Other Study ID Numbers: AG0031, K23AG019161, K23AG1916101A1, 5P30DK019525
Study First Received: July 19, 2005
Last Updated: March 9, 2010
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Insulin Resistance
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Leuprolide
Metformin
Testosterone
Androgens
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014